Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Assembling cells into artificial 3-D microtissues, including a tiny gland

06.03.2009
Hybridized DNA is glue that sticks these cells together to resemble real tissue

As synthetic biologists cram more and more genes into microbes to make genetically engineered organisms produce ever more complex drugs and chemicals, two University of California chemists have gone a step further.

They have assembled different types of genetically engineered cells into synthetic microtissues that can perform functions such as secreting and responding to hormones, promising more complex biological capabilities than a single cell alone could produce.

"This is like another level of hierarchical complexity for synthetic biology," said coauthor Carolyn Bertozzi, UC Berkeley professor of chemistry and of molecular and cell biology and director of the Molecular Foundry at Lawrence Berkeley National Laboratory. "People used to think of the cell as the fundamental unit. But the truth is that there are collections of cells that can do things that no individual cell could ever be programmed to do. We are trying to achieve the properties of organs now, though not yet organisms."

While the synthetic tissues today comprise only a handful of cells, they could eventually be scaled up to make artificial organs that could help scientists understand the interactions among cells in the body and might some day substitute for human organs.

"We are really taking this into the third dimension now, which for me is particularly exciting," said first author Zev J. Gartner, a former UC Berkeley post-doctoral fellow who recently joined the UC San Francisco faculty as an assistant professor of pharmaceutical chemistry. "We are not simply linking cells together, we are linking them together in 3-D arrangements, which introduces a whole new level of cellular behavior which you would never see in 2-D environments."

Gartner and Bertozzi, the T.Z. and Irmgard Chu Distinguished Professor at UC Berkeley and a Howard Hughes Medical Institute investigator, report on their assembly of three-dimensional microtissues this week in the online early edition of the journal Proceedings of the National Academy of Sciences.

One type of cell that needs other cells to make it work properly is the stem cell, Bertozzi noted. Theoretically, using Gartner and Bertozzi's chemical technique, it should be possible to assemble stem cells with their helper cells into a functioning tissue that would make stem cells easier to study outside the body.

"In principal, we might be able to build a stem cell niche from scratch using our techniques, and then study those very well defined structures in controlled environments," Bertozzi said.

Bertozzi noted that most of the body's organs are a collection of many cell types that need to be in actual physical contact to operate properly. The pancreas, for example, is a collection of specialized cells, including insulin-secreting beta cells, that "sense glucose from the environment and respond by producing insulin. A complex feedback regulatory loop goes into all of this, and you need more than one cell type to achieve such regulation."

"If you really want to understand the way these cells behave in an organism, especially a human, you would like to recapitulate that environment as closely as possible in vitro," Gartner said. "We are trying to do that, with the aim that the rules we learn may help us control them better."

Gartner and Bertozzi assembled three types of cultured cells into onion-like layers by using two established technologies: DNA hybridization and Staudinger chemistry. DNA hybridization is like a "programmable glue," she said, that can stick cells together because of the highly precise nature of binding between complementary DNA strands: One strand of the DNA helix binds only to its complementary strand and nothing else. By putting a short DNA strand on the surface of one cell and its complementary strand on another cell, the researchers assure that the two lock together exclusively.

To get these specific DNA strands onto the cells, they used chemical reactions that do not interfere with cellular chemistry but nevertheless stick desired chemicals onto the cell surface. The technique for adding unusual but benign chemicals to cells was developed by Bertozzi more than a decade ago based on a chemical reaction called the Staudinger ligation.

After proving that they could assemble cells into microtissues, Gartner and Bertozzi constructed a minute gland – analogous to a lymph node, for example – such that one cell type secreted interleukin-3 and thereby kept a second cell type alive.

"What we did is build a little miniaturized, stripped-down system that operates on the same principle and looks like a miniaturized lymph node, an arrangement where two cells communicate with each another and one requires a signal from the other," she said. "The critical thing is that the two cells have to have a cell junction. If you just mix the cells randomly without connection, the system doesn't have the same properties."

She expects that eventually, clusters could be built on clusters to make artificial organs that someday may be implanted into humans.

"Our method allows the assembly of multicellular structures from the bottom up. In other words, we can control the neighbors of each individual cell in a mixed population," she said. "By this method, it may be possible to assemble tissues with more sophisticated properties."

One interesting aspect of the technique is that DNA hybridization seems to be temporary, like a suture. Eventually, the cells may substitute their own cell-cell adhesion molecules for the DNA, creating a well-knit and seemingly normal, biological system.

Robert Sanders | EurekAlert!
Further information:
http://www.berkeley.edu

More articles from Life Sciences:

nachricht Warming ponds could accelerate climate change
21.02.2017 | University of Exeter

nachricht An alternative to opioids? Compound from marine snail is potent pain reliever
21.02.2017 | University of Utah

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Impacts of mass coral die-off on Indian Ocean reefs revealed

21.02.2017 | Earth Sciences

Novel breast tomosynthesis technique reduces screening recall rate

21.02.2017 | Medical Engineering

Use your Voice – and Smart Homes will “LISTEN”

21.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>